A research team including Graduate Student Jumpei Tagawa at the Department of Materials Science and Engineering, School of Materials and Chemical Technology, Institute of Science Tokyo, and Associate Professor Saeko Yanaka at the Materials & Structures Laboratory, Institute of Integrated Research, Institute of Science Tokyo, has announced the creation of monoclonal antibodies that can work against the major norovirus strain GII.4 and the emerging strain GII.17. The team successfully clarified the binding mechanism with the virus at a molecular level. These results are expected to lead to new strategies for developing mutation-resistant antibodies and designing next-generation vaccines. The findings were published in the journal Protein Science on March 12.
Norovirus causes about 700 million infections and 219,000 deaths per year worldwide, and the medical and social cost is estimated to be $60 billion per year. In particular, the GII.4 strain has been prevalent worldwide over the past 20 years, and the emerging strain GII.17, which was prevalent in the winter of 2014, is more infectious than the GII.4 strain.
The virus is classified as an RNA virus, and its outer shell is a dense structure consisting of 180 capsid proteins. This structure is a complex target for the immune system and has proven difficult to neutralize by antibodies.
Conventional antibody studies have mainly analyzed IgG antibodies. In this study, the research group focused on "multivalency," a property of IgM antibodies in which one antibody molecule has multiple antigen-binding domains due to the 10 antigen-binding domains (Fab). Monoclonal antibodies that work against GII.4 and the emerging strain GII.17 were produced and the mechanism of binding enhancement was quantitatively investigated.
Real-time visualization of IgM antibodies binding at multiple points while scanning the surface of virus-like particles using a high-speed atomic force microscope confirms that the multivalent structure forms multiple binding points on the virus surface and maintains stable binding.
Next, interaction analysis using surface plasmon resonance revealed that IgM binding is enhanced up to one hundredfold in environments with high antigen density. This phenomenon of using multiple binding sites at the same time to produce a very strong binding force as a whole (avidity effect) indicates that even if a single Fab region has low affinity for the virus, utilizing multiple points allows IgM to achieve high binding strength comparable to IgG antibodies.
By leveraging IgM's binding mode and multivalency, which differ from those of IgG, it may be possible to develop antibodies resistant to viral mutations and vaccines that work across a broad range of strains.
Yanaka stated: "In this study, we 'visualized' the multivalency of IgM antibodies and quantitatively demonstrated their binding-strengthening effect for the first time. We believe that understanding how they act cooperatively at multiple points, rather than just relying on a single point of strength, will lead to the design of mutation-resistant antibodies and next-generation vaccines. Moving forward, we hope to advance social implementation with an eye toward applying this to other viruses as well."
Journal Information
Publication: Protein Science
Title: Characterization of high affinity IgM and IgG monoclonal antibodies against norovirus variants GII.4 and GII.17
DOI: 10.1002/pro.70522
This article has been translated by JST with permission from The Science News Ltd. (https://sci-news.co.jp/). Unauthorized reproduction of the article and photographs is prohibited.